J Neurol DOI 10.1007/s00415-015-7639-1
LETTER TO THE EDITORS
MuSK myasthenia gravis as a manifestation of immune restoration disease in an HIV-positive patient Karthik Ragunathan • Bandana Pathak Kumud Dahal
•
Received: 8 December 2014 / Revised: 1 January 2015 / Accepted: 3 January 2015 Ó Springer-Verlag Berlin Heidelberg 2015
Dear Sirs, A 39-year-old African American female with established HIV infection presented to the infectious diseases’ clinic with new symptoms of voice change, drooping of eyelids and blurring of vision. Her other symptoms included progressive dysphagia, dyspnea and intermittent aspiration of 6 months duration. She was on a salvage anti-retroviral therapy of tenofovir/emtricitabine 300 mg OD, boosted darunavir 600 mg BID and raltegravir 400 mg BID for the last 12 months with CD4 count below 100 at the time of initiation of this regimen. Her examination was significant for left sided ptosis, decreased upgaze bilaterally and decreased abduction of right eye. Facial muscles were weak with sardonic smile. Voice was mildly dysphonic with nasal component. Motor, sensory, coordination, deep tendon reflexes were normal. Her initial workup showed a CD4 count of 520 with an undetectable HIV viral load. An elaborative workup was negative for anti-DS DNA, anti-smith, U1-ribonucleoprotein, myositis-specific Jo1, anti-topoisomerase I, Hepatitis C antibody, lyme serology and rapid plasma reagin. She was referred to neurology for further evaluation. Her MRI of her brain with and without
K. Ragunathan (&) Department of Internal Medicine, University of Illinois College of Medicine, 637 NE Glen Oak Ave, Peoria, IL 61637, USA e-mail: [email protected] B. Pathak OSF Saint Francis Medical Center, Peoria, IL, USA K. Dahal Department of Infectious Diseases, University of Illinois College of Medicine, Peoria, IL, USA
contrast did not show any acute neurological findings. EMG/NCS showed normal findings except mild left carpal tunnel syndrome. Initial clinical impression at this time was myasthenia gravis (MG). However, blood work was negative for acetylcholine receptor antibody (AChR Ab), creatine phosphokinase enzyme and aldolase enzyme. MuSK antibody was strongly positive at 1:2,560. She was started on prednisone 60 mg/day with subsequent significant improvement of her weakness, dysphagia and visual acuity. After 1 month, she was started on azathioprine at 50 mg every 12 h along with prednisone at 40 mg/day. Nearly after 1 month of starting azathioprine, patient had experienced difficulty in chewing, blurring of vision and increased dyspnea. She was hospitalized and underwent 5 days of plasma exchange. All her symptoms completely resolved at the end of plasmapheresis except persistent mild ptosis. Her prednisone dose was increased to 60 mg/day at the time of discharge. Our case represents a rare entity of MuSK positive myasthenia in HIV patients treated with ART. It may be associated with immune restoration disease (IRD) due to the restoration of dysregulated immune response against pathogen specific antigens [1]. However, various autoimmune diseases such as graves disease, systemic lupus erythematosus have been reported during the IRD phase. MuSK is a receptor tyrosine kinase that mediates agrindependent AChR clustering and neuromuscular junction formation during development. Anti-MuSK have been detected in around half the patients with AChR-Ab generalized negative MG. Clinical features of MuSK resemble AChR-Ab myasthenia but these patients may additionally have increased incidence of diplopia, ptosis, dysarthria, prominent respiratory muscle weakness and are less responsive to acetylcholinesterase inhibitors [2]. Mainstay
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of treatment for MuSK MG is plasma exchange and immunosuppressives. There are two previous published case reports of antiMuSK myasthenia gravis in HIV-infected patients, successfully treated with rituximab and cyclosporine [3, 4]. Knopf et al. [5] reported a case of myasthenia gravis in a similar setting of HIV treatment that responded to treatment with pyridostigmine and azathioprine. Our patient initially responded to prednisone and azathioprine but had an exacerbation requiring treatment with plasma exchange. Our case scenario emphasizes the importance of recognition of autoimmune disorders as a manifestation of immune reconstitution in HIV-infected patients receiving antiretroviral therapy. Conflicts of interest On behalf of all authors, the corresponding author states that there is no conflict of interest. Ethical standard The patient consented to the treatment in the hospital. This is a case study and hence no ethical approval was obtained from the hospital ethics committee.
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References 1. French MA (2009) Immune reconstitution inflammatory syndrome: a reappraisal. Clin Infect Dis 48(1):101–107 2. Sanders DB, El-Salem K, Massey JM, McConville J, Vincent A (2003) Clinical aspects of MuSK antibody positive seronegative MG. Neurology 60(12):1978–1980 3. Kuntzer T, Carota A, Novy J, Cavassini M, Du Pasquier RA (2011) Rituximab is successful in an HIV-positive patient with MuSK myasthenia gravis. Neurology 76(8):757–758. doi:10.1212/ WNL.0b013e31820d6290 4. Kurokawa T, Nishiyama T, Yamamoto R, Kishida H, Hakii Y, Kuroiwa Y (2008) Anti-MuSK antibody positive myasthenia gravis with HIV infection successfully treated with cyclosporin: a case report. Rinsho Shinkeigaku 48:666–669 5. Knopf L, Menkes DL (2010) Comorbid HIV and myasthenia gravis: case report and review of the literature. J Clin Neuromuscul Dis 12(2):80–84
LETTER TO THE EDITORS
MuSK myasthenia gravis as a manifestation of immune restoration disease in an HIV-positive patient Karthik Ragunathan • Bandana Pathak Kumud Dahal
•
Received: 8 December 2014 / Revised: 1 January 2015 / Accepted: 3 January 2015 Ó Springer-Verlag Berlin Heidelberg 2015
Dear Sirs, A 39-year-old African American female with established HIV infection presented to the infectious diseases’ clinic with new symptoms of voice change, drooping of eyelids and blurring of vision. Her other symptoms included progressive dysphagia, dyspnea and intermittent aspiration of 6 months duration. She was on a salvage anti-retroviral therapy of tenofovir/emtricitabine 300 mg OD, boosted darunavir 600 mg BID and raltegravir 400 mg BID for the last 12 months with CD4 count below 100 at the time of initiation of this regimen. Her examination was significant for left sided ptosis, decreased upgaze bilaterally and decreased abduction of right eye. Facial muscles were weak with sardonic smile. Voice was mildly dysphonic with nasal component. Motor, sensory, coordination, deep tendon reflexes were normal. Her initial workup showed a CD4 count of 520 with an undetectable HIV viral load. An elaborative workup was negative for anti-DS DNA, anti-smith, U1-ribonucleoprotein, myositis-specific Jo1, anti-topoisomerase I, Hepatitis C antibody, lyme serology and rapid plasma reagin. She was referred to neurology for further evaluation. Her MRI of her brain with and without
K. Ragunathan (&) Department of Internal Medicine, University of Illinois College of Medicine, 637 NE Glen Oak Ave, Peoria, IL 61637, USA e-mail: [email protected] B. Pathak OSF Saint Francis Medical Center, Peoria, IL, USA K. Dahal Department of Infectious Diseases, University of Illinois College of Medicine, Peoria, IL, USA
contrast did not show any acute neurological findings. EMG/NCS showed normal findings except mild left carpal tunnel syndrome. Initial clinical impression at this time was myasthenia gravis (MG). However, blood work was negative for acetylcholine receptor antibody (AChR Ab), creatine phosphokinase enzyme and aldolase enzyme. MuSK antibody was strongly positive at 1:2,560. She was started on prednisone 60 mg/day with subsequent significant improvement of her weakness, dysphagia and visual acuity. After 1 month, she was started on azathioprine at 50 mg every 12 h along with prednisone at 40 mg/day. Nearly after 1 month of starting azathioprine, patient had experienced difficulty in chewing, blurring of vision and increased dyspnea. She was hospitalized and underwent 5 days of plasma exchange. All her symptoms completely resolved at the end of plasmapheresis except persistent mild ptosis. Her prednisone dose was increased to 60 mg/day at the time of discharge. Our case represents a rare entity of MuSK positive myasthenia in HIV patients treated with ART. It may be associated with immune restoration disease (IRD) due to the restoration of dysregulated immune response against pathogen specific antigens [1]. However, various autoimmune diseases such as graves disease, systemic lupus erythematosus have been reported during the IRD phase. MuSK is a receptor tyrosine kinase that mediates agrindependent AChR clustering and neuromuscular junction formation during development. Anti-MuSK have been detected in around half the patients with AChR-Ab generalized negative MG. Clinical features of MuSK resemble AChR-Ab myasthenia but these patients may additionally have increased incidence of diplopia, ptosis, dysarthria, prominent respiratory muscle weakness and are less responsive to acetylcholinesterase inhibitors [2]. Mainstay
123
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of treatment for MuSK MG is plasma exchange and immunosuppressives. There are two previous published case reports of antiMuSK myasthenia gravis in HIV-infected patients, successfully treated with rituximab and cyclosporine [3, 4]. Knopf et al. [5] reported a case of myasthenia gravis in a similar setting of HIV treatment that responded to treatment with pyridostigmine and azathioprine. Our patient initially responded to prednisone and azathioprine but had an exacerbation requiring treatment with plasma exchange. Our case scenario emphasizes the importance of recognition of autoimmune disorders as a manifestation of immune reconstitution in HIV-infected patients receiving antiretroviral therapy. Conflicts of interest On behalf of all authors, the corresponding author states that there is no conflict of interest. Ethical standard The patient consented to the treatment in the hospital. This is a case study and hence no ethical approval was obtained from the hospital ethics committee.
123
References 1. French MA (2009) Immune reconstitution inflammatory syndrome: a reappraisal. Clin Infect Dis 48(1):101–107 2. Sanders DB, El-Salem K, Massey JM, McConville J, Vincent A (2003) Clinical aspects of MuSK antibody positive seronegative MG. Neurology 60(12):1978–1980 3. Kuntzer T, Carota A, Novy J, Cavassini M, Du Pasquier RA (2011) Rituximab is successful in an HIV-positive patient with MuSK myasthenia gravis. Neurology 76(8):757–758. doi:10.1212/ WNL.0b013e31820d6290 4. Kurokawa T, Nishiyama T, Yamamoto R, Kishida H, Hakii Y, Kuroiwa Y (2008) Anti-MuSK antibody positive myasthenia gravis with HIV infection successfully treated with cyclosporin: a case report. Rinsho Shinkeigaku 48:666–669 5. Knopf L, Menkes DL (2010) Comorbid HIV and myasthenia gravis: case report and review of the literature. J Clin Neuromuscul Dis 12(2):80–84
